Establishment and
cidofovir sensitivity of a cell line from a heart transplant recipient with
multiple cutaneous tumors.

A new cell line, designated as Tuwei00, is described. It originated from an
Epstein-Barr virus-positive skin tumor biopsy of a heart transplant recipient,
whose numerous cutaneous neoplasms were treated with the antiviral drug
cidofovir what caused at least transient remissions. The cell line was
established in vitro and maintained for more than 70 passages. Cells of early
passages were characterized by a slower growth, the inability to form colonies
and a higher sensitivity to cidofovir. After overcoming a crisis, the cells grew
faster, to a higher density and were able to form adherent colonies from single
cells as well as colonies in soft agar. Chromosome analysis showed
diploidy/hyperdiploidy at the earlier and hypodiploidy at the later passages.
Sensitivity to cidofovir was distinctly higher in early passages of Tuwei00
cells than in later passages and was characterized by distinct decline of cell
survival after long term cidofovir exposure. Established normal human
keratinocytes, HaCaT cells, which were checked for comparison, showed a low
cidofovir sensitivity similar to late passage Tuwei00 cells.

Neoplasma. 2003; 50(3): 165-171.

Efficacy and
toxicity of low-dose melphalan in myelodysplastic syndromes and acute myeloid
leukemia with multilineage dysplasia.

Effective therapy of myelodysplatic syndromes and acute myeloid leukemia
originating from myelodysplastic syndrome has remained an unresolved problem.
Advanced age of the patients and persistent pancytopenia make the treatment
difficult. Despite large number of therapeutic options none of them is
satisfactory. Recently palliative treatment with low-dose melphalan has been
reported to have certain activity. The aim of the study was to evaluate the
efficacy of low-dose melphalan in high-risk myelodysplastic syndromes (MDS) and
acute myeloid leukemia with multilineage dysplasia (AML). Twenty three patients
were eligible for the study: 8 with MDS and 15 with AML with multilineage
dysplasia. All of them received oral melphalan in a daily dose of 2 mg. Median
total dose of the drug was 120 mg (40-840 mg). Ten patients responded to the
therapy. We observed complete remission (CR) in 4, partial remission (PR) in 3
and stabilization of the disease in 3 patients. Thirteen patients did not
respond to the therapy. The survival time of the patients from the day of
diagnosis and from the beginning of the treatment with melphalan was longer in
patients responding to the therapy (median 15 and 10 months, respectively) than
in non-responders (4.5 and 4 months, p=0.003 and p=0.008, respectively).
Low-dose melphalan shows significant activity in high-risk MDS and AML with
multilineage dysplasia with acceptable toxicity.

Neoplasma. 2003; 50(3): 172-175.

Administration of
liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) and diclofenac in
the combination attenuates their anti-tumor activities.

The anti-tumor effects of i.p. administered cyclooxygenase inhibitor -
diclofenac and i.v. administered liposomal muramyl tripeptide
phosphatidylethanolamine (MTP-PE) were investigated using a s.c. growing murine
fibrosarcoma tumor. Tumor growth was assessed by measuring tumor volumes and
survival of the mice. Both of the drugs were administered either alone or in
combination. Repeated application of diclofenac in two schedules (150
microg/mouse/day for 14 consecutive days or 2 x 150 microg/mouse/week for 4
weeks) or application of liposomal MTP-PE (2 x 20 microg/mouse/week for 4 weeks)
starting on day 5 after tumor cell transplantation significantly suppressed the
tumor growth and increased the percentage of surviving mice. However, the volume
of tumors and the survival time in tumor bearing mice treated with the two
agents were similar to untreated counterparts. Thus, these data suggest the
anti-tumor activity of either of the two drugs is lost when they are used in
combination. Hematological examinations confirmed previously observed
hematopoiesis-stimulating activities of the drugs when given alone. However,
mutually potentiating effects after combined administration of liposomal MTP-PE
and diclofenac were observed only exceptionally. Our findings corroborate the
recommendation that the interactions of drugs used for the treatment of tumors
must be carefully checked, if the drugs are applied in combination.

The association between Helicobacter pylori and gastric cancer has been debated
in the last decade and evidence for such a causal relationship has been claimed.
This study aimed to detect the seroprevalence of Helicobacter pylori in patients
with gastric cancer and compare it to the other cancer patients. In addition,
the value of IgG and IgA in Helicobacter pylori detection was compared in
patients with gastric cancer. Consecutive gastric and other cancer patients
treated between 1999-2001 were prospectively studied. Serum Helicobacter pylori
IgG and IgA levels were determined. Serological tests revealed IgA and IgG
positivity as 53.9% and 50.9%, respectively, while 74.5% had positive results
for either IgA or IgG. Serum IgA positivity was significantly higher in gastric
cancer group compared to control group (p=0.02). In contrast, serum IgG
positivity did not show a significant difference in both groups and either IgG
or IgA seropositivity was significantly higher in patients with gastric cancer
compared to control patients (p=0.04). This study revealed a higher
seroprevalence of Helicobacter pylori in gastric cancer patients and IgA was a
better predictor of Helicobacter pylori seropositivity in gastric cancer
patients.

Neoplasma. 2003; 50(3): 185-190.

The evaluation of
left ventricular function in childhood cancer survivors by pharmacological
stress echocardiography.

Elbl L, Hrstkova H, Chaloupka V, Novotny J, Michalek J.

Department of Cardiopulmonary Testing, Faculty Hospital Brno, 639 00
Brno, Czech Republic. lelbl@fnbrno.czLate cardiotoxicity after anthracycline chemotherapy for childhood cancer is
well recognized sequelae. Many long-term survivors may have subclinical cardiac
dysfunction undetectable at a baseline evaluation. Various tests have been
utilized for the diagnosis of left ventricular impairment. Recently, low-dose
dobutamine stress echocardiography has been proposed as a more sensitive
screening test. We have applied low-dose dobutamine stress echocardiography
(5-10 microg/kg/min) in 36 asymptomatic survivors (20 male/16 female aged
14.6+/-4.7 years) treated with a cumulative dose of 226+/-106 mg/m2 of
doxorubicin. The median follow-up was 5 years. Control group consisted of 20 sex
and age matched volunteers (12 male/8 female aged 12.6+/-4.9 years). We found
significant differences in mean velocity of circumferential fibre shortening,
myocardial performance index (Tei index), left ventricular posterior wall
thickening and endsystolic wall stress at a baseline. The stress response was
significantly blunted only in a patient group in the following parameters:
endsystolic wall stress, isovolumic relaxation time and myocardial performance
index. The threshold response was abnormal (0-5% improvement of a variable only)
in 45% of subjects from a control group in one or two parameters. On the
contrary, 63% of subjects from a patient group responded pathologically (the
worsening of a variable) in one or more parameters. We have not found a good
correlation between risk factors of late cardiotoxicity and stress changes of
left ventricular function parameters. Low-dose dobutamine stress
echocardiography is safe and feasible diagnostic tool in children and
adolescents. Dobutamine significantly increases the differences in cardiac
variables between healthy population and asymptomatic survivors for childhood
cancer. In comparison to the controls, most asymptomatic patients revealed
subclinical myocardial damage at test. The predictive value for the development
of clinical symptoms and cardiac complications need to be assessed in a large
prospective study.

Department of Toxicology and Carcinogenesis, The Nofer Institute of
Occupational Medicine, 90-950 Lodz, Poland. mstep@imp.lodz.plHuman non-small-cell lung cancers (NSCLCs) of 48 patients were analyzed
immunohistochemically to detect P21 ras and P53 proteins expression. The
relationship between P21 ras and P53 proteins expression and clinicopathologic
findings was also assessed. DAKO EnVision TM detection system was employed in
the study. The P21 ras and P53 proteins expression was shown in 75% (36/48) and
33.3% (16/48) studied NSCLCs, respectively. In both cases the difference was
significant when compared with adequate negative control. Simultaneous
expression of both studied proteins was observed in all cases in which P53
expression was noticed. No significant association of P21 ras and P53 expression
was found with age, histologic type, histologic grade, tumor size or lymph node
metastasis of the studied NSCLCs. Therefore, our study suggests that P21 ras and
P53 protein play a role in the pathogenesis of NSCLCs but they have no value as
a prognostic markers in the case of lung cancers.

Department of Medical Oncology, Hospital Arnau de Vilanova, 46015
Valencia, Spain. juan_osc@gva.esPlatinum-based combinations are efficacious in the treatment of advanced
non-small cell lung cancer (NSCLC) but their toxicity makes them unsuitable for
elderly and for patients with co-morbidities. We assessed the efficacy and
toxicity of low-dose of paclitaxel in patients who were elderly or who had
contraindications against cisplatin therapy. Seventy-one patients (median age
68; range 42-82 years) with unresectable NSCLC were treated with weekly
paclitaxel (80 mg/m2) infusion (1 h) for several cycles without intervening rest
periods. Thirty-seven patients had PS 1 and 34 had PS 2 status. A total of 614
courses were administered (median 9, range 2-20). There were no episodes of
grade 4 toxicities and only 1 patient had grade 3 thrombopenia. Grade 3 anemia
or neutropenia were not observed and severe non-hematological toxicity was
uncommon: grade 1-2 fatigue in 52%; grade 1-2 motor neuropathy in 42% and grade
3 in 5.5%; grade 1-2 sensory neuropathy in 46.3% of patients. Twenty-seven of
the 67 evaluable patients (40.3%) had an objective response, whereas 26 patients
(38.8%) had stable disease. The median overall survival for the entire group was
8.4 months (95% CI = 5.6 to 11.2) and the 1-year and 2-year survival was 37.4%
and 12.1%, respectively. The median time-to-progression was 5.4 months (95% CI =
3.3 to 7.4). Our data show that low-dose weekly paclitaxel is active and well
tolerated in this group of patients with NSCLC and poor prognosis and, as such,
is useful for patients in whom platinum-based combinations are not suitable.

The value of
18F-fluorodeoxyglucose positron emission tomography with the additional help of
tumor markers in cancer screening.

Cancer screening is a major healthcare issue. Screening modalities are
constantly changing due to improvements in technology. Whole body positron
emission tomography (PET) with 18F-fluoro-2 deoxy-D-glucose (FDG) and the
additional help of the serum levels of tumor markers have been considered as
non-invasive methods for cancer screening in asymptomatic subjects. A total of
1283 subjects underwent whole-body FDG PET studies with the additional help of
the serum levels of tumor markers in our center for cancer screening. The final
diagnoses were confirmed by other imaging modalities or pathological findings in
subjects with positive FDG-PET findings, and follow-up for at least 6 months
were held in subjects with negative FDG-PET findings. Among a total of 18 (1.4%)
subjects with cancers, FDG-PET detected cancers in 15 (1.2%) subjects but with
false negative studies in 3 subjects with hepatoma (AFP = 129.6 ng/ml), prostate
cancer (PSA = 25.1 ng/ml), and breast cancer (CEA and CA-153 were normal).
False-positive FDG-PET studies were found in 24 (1.9%) subjects. However, none
had abnormal serum levels of tumor markers. Whole body FDG-PET with the
additional help of tumor markers could reduce the false negative and false
positive results of FDG-PET only.

The aim of our study was to compare the usefulness of thallium-201 (Tl-201)
single photon emission computed tomography (SPECT) mammoscintigraphy and
ultrasonography to detect breast cancer in mammographical dense breasts. This
study included 32 Taiwanese female patients with indeterminate mammographic
probability of malignancy due to mammographical dense breasts. Both Tl-201 SPECT
mammoscintigraphy and ultrasonography were performed for each patient. Then, all
of the 32 breast masses undervent biopsies or operations to obtain finally
pathological diagnoses. Based on the finally pathological diagnoses, 24 masses
were breast cancer and 8 masses were benign breast tumors among the 32 patients.
Twenty-two cancers and one benign tumor had positive Tl-201 SPECT
mammoscintigraphic findings. The sensitivity, specificity, and accuracy were
92%, 88%, and 91%. Twenty-two cancers and 5 benign tumors had positive
ultrasonographic findings. The sensitivity, specificity, and accuracy were 92%,
38%, and 78%, respectively. To detect breast cancer in patients with
non-diagnostic mammogram because of mammographically dense breasts, Tl-201 SPECT
mammoscintigraphy and ultrasonography have the same sensitivity to screen breast
masses. However, due to its higher specificity, Tl-201 SPECT mammoscintigraphy
should be useful to confirm the ultrasonographic findings.

Megestrol acetate (MA) is a progestational agent, currently known as one of
the most effective appetite stimulants in patients suffering from cancer
anorexia/cachexia syndrome. Oral suspension of this drug may be particularly
useful in patients with far advanced disease, where taking larger amount of
pills may lead to the decrease of patient compliance. The influence of oral MA
suspension on quality of life and nutritional status was evaluated in 22
patients with far advanced cancer suffering from anorexia and more than 5 per
cent weight loss, all beyond the scope of anticancer treatment. Most patients
had lung or gastrointestinal cancer. QLQ-C30 questionnaire, visual analogue
scale (VAS) for appetite, anthropometry, maximal handgrip strength and
laboratory data were obtained before treatment and then after 2, 4, and 8 weeks
of therapy. Despite of a known high mortality in this prognostically unfavorable
group of patients (36% within two months in this study), overall quality of life
after the daily dose of 480-840 mg of MA was improved in 63, 56, and 55% of
patients remaining on therapy after 2, 4, and 8 weeks, respectively. Appetite
was the most successfully influenced parameter with an improvement in VAS in 95%
of cases after 2 weeks of therapy (p=0.0001). The drug was well tolerated by the
great majority of patients. Oral suspension of megestrol acetate maybean
effective palliative treatment for many patients with far advanced cancer
suffering from anorexia/cachexia syndrome.

To examine the relation of the total intake of fluids and the types of
beverages to the risk of bladder cancer, we conducted a hospital based
case-control study with 130 newly diagnosed bladder cancer patients and the same
number of matched controls. Information of total fluid intake was derived from
the reported frequency of consumption of the different types of beverages on the
food frequency questionnaire. Univariate and multivariate logistic regression
analyses were performed in statistical analysis. There was no statistically
significant difference between the cases and the controls in total daily fluid
intake. Multivariate logistic regression model showed consumption of: soda
(OR=8.32; 95%CI=3.18-21.76), coffee (OR=1.46; 95%CI=1.05-2.01) and spirits
(OR=1.15; 95%CI=1.04-1.28) as statistically significant risk factors, while
mineral water (OR=0.52; 95%CI=0.34-0.79), skim milk (OR=0.38; 95%CI=0.16-0.91),
yogurt (OR=0.34; 95%CI=0.12-0.97) and frequency of daily urination (OR=0.27;
95%CI=0.18-0.41) were statistically significant protective variables. In our
study no statistically significant association was observed for total fluid
intake. The findings suggest consumption of soda, coffee and spirits were
indicated as a risk factors for bladder cancer, while mineral water, skim milk,
yogurt and frequency of urination as protective factors for bladder cancer.